Although the pulmonary artery is an artery by definition since it carries blood away from the heart, it is a vein both structurally and functionally. Its wall thickness is similar to that of veins and it carries de-oxygenated blood at low pressure of less than 20 mmHg, which is significantly lower than the blood pressure in the arteries.
In pulmonary hypertension, the blood pressure in the pulmonary artery generally exceeds 25 mmHg at rest and 30 mmHg with exercise. This is mostly due to vasoconstriction of the pulmonary artery. Sustained elevated pulmonary vascular constriction and resistance to blood flow leads to the thickening of the pulmonary arterial walls, which sustains the elevated pressure. This condition is known as pulmonary arterial hypertension or PAH. In PAH, the pulmonary arteries show medial hypertrophy, intimal fibrosis, and plexiform lesions. Pumping the blood against increased resistance leads to right heart failure and death within two to three years.
Two common types of pulmonary artery hypertension exist: primary or idiopathic that is associated with thickened pulmonary arteries with very high pulmonary pressures (≈80/50) and secondary or hypoxic that is characterized by moderate pulmonary pressures (≈50/30).
Serotonin (5-Hydroxytryptamine, 5-HT) appears be involved in the etiology of elevated pulmonary arterial pressure (PAH), including its initiation and partial maintenance. Support for this includes the following:                1. Mice over-expressing the 5-hydroxytryptamine-transporter gene develop spontaneous and progressive pulmonary hypertension.        2. 5-HT causes contraction of the pulmonary artery.        3. Trophic action of 5-HT2A receptors in cardiomyocytes and the beneficial effects of ketanserin (a 5-HT2A serotonin blocker) in cardiac hypertrophy. Cardiac hypertrophy induced even by isoproterenol (a β-adrenergic receptor agonist) requires stimulation of 5-HT2A receptors.        4. Effects of dexfenfluramine in causing pulmonary hypertension are mediated by 5-HT2B receptors.        5. Hypoxia-induced rise in plasma serotonin possibly mediates the hypoxia induced pulmonary hypertension via stimulation of 5-HT2B receptors.        6. Total pulmonary resistance is correlated with plasma serotonin levels in pulmonary hypertensive animals and patients.        7. Hypoxia-induced vascular proliferation required the 5-HT2A receptor activity.        8. Nitric oxide (NO) is lacking in the pulmonary arteries of PAH patients. NO appears to be the final common mediator of vaso-relaxation. Serotonin reduces the levels of nitric oxide in vascular smooth muscle cells.        9. Pulmonary hypoxia results in red blood cell sickling, increased vascular adhesions and the release of serotonin from blood platelets which often lead to PAH.        
The vasoconstrictor effects of serotonin, triggered through the 5-HT2B receptors, appear to be the initial triggers of the disease, which can be prevented by 5-HT2B antagonists. 5-HT levels are increased 10-30 times normal in patients with PAH and the 5-HT2B receptor population is increased ˜3.5× in the pulmonary artery of patients with PAH.
Chronic PAH is partially maintained by physical and fixed alterations in the structure of walls of the small pulmonary arteries and arterioles. These changes which are induced to withstand the increased pressure and include vascular endothelial and smooth muscle cell proliferation, medial, predominantly smooth muscle cell, thickening, neo-intimal formation, and the subsequent obliteration of the vascular lumen. These effects appear to be mediated by 5-HT2A receptors.
Thus, serotonin appears to be involved in both the initiation, through vasoconstriction (5-HT2B receptors), and maintenance, through arterial wall thickening (5-HT-2A receptors) of PAH.
To ensure both prevention and treatment of PAH, both 5-HT2A and 5-HT2B receptors need to be blocked.